Abstract：
Stalling of ribosomes engaged in protein synthesis can lead to significant defects in the function of newly synthesized proteins and thereby impair protein homeostasis. Consequently, partially synthesized polypeptides resulting from translation stalling are recognized and eliminated by several quality control mechanisms. First, if translation elongation reactions are halted prematurely, a quality control mechanism called ribosome-associated quality control (RQC) initiates the ubiquitination of the nascent polypeptide chain and subsequent proteasomal degradation. Additionally, when ribosomes with defective codon recognition or peptide-bond formation stall during translation, a quality control mechanism known as non-functional ribosomal RNA decay (NRD) leads to the degradation of malfunctioning ribosomes. In both of these quality control mechanisms, E3 ubiquitin ligases selectively recognize ribosomes in distinct translation-stalling states and ubiquitinate specific ribosomal proteins. Significant efforts have been devoted to characterize E3 ubiquitin ligase sensing of ribosome \'collision\' or \'stalling\' and subsequent ribosome is rescued. This article provides an overview of our current understanding of the molecular mechanisms and physiological functions of ribosome dynamics control and quality control of abnormal translation.
摘要：
参与蛋白质合成的核糖体的停滞可导致新合成蛋白质功能的显著缺陷,从而损害蛋白质稳态。因此,由翻译停滞产生的部分合成的多肽被几种质量控制机制识别和消除。首先,如果翻译延伸反应过早停止，称为核糖体相关质量控制（RQC）的质量控制机制启动新生多肽链的泛素化和随后的蛋白酶体降解。此外,当具有缺陷密码子识别或肽键形成的核糖体在翻译过程中停滞时，一种称为非功能性核糖体RNA衰变（NRD）的质量控制机制会导致功能不良的核糖体降解。在这两种质量控制机制中，E3泛素连接酶选择性识别处于不同翻译停滞状态的核糖体并泛素化特定核糖体蛋白。已经做出了巨大的努力来表征E3泛素连接酶对核糖体“碰撞”或“停滞”的感知，并挽救了随后的核糖体。本文概述了我们目前对核糖体动力学控制和异常翻译质量控制的分子机制和生理功能的理解。
